From the Journals

Do carbs drive obesity? With evidence inconclusive, debate continues



Are refined and processed carbohydrates particularly fattening? Or is a calorie just a calorie, regardless of whether the source is carbohydrate, protein, or fat?

While the debate continues, David S. Ludwig, MD, PhD, and Cara B. Ebbeling, PhD, argued in a recent clinical review that diet does indeed affect metabolism and body composition.

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While evidence from human studies remains limited, animal research findings are consistent with a carbohydrate-insulin model of obesity, according to Dr. Ludwig and Dr. Ebbeling, who are with the New Balance Foundation Obesity Prevention Center at Boston Children’s Hospital and Harvard Medical School.

The carbohydrate-insulin model holds that eating processed, high–glycemic load carbohydrates causes hormonal changes that promote calorie deposition in fat tissue, aggravate hunger, and reduce energy expenditure, they said in JAMA Internal Medicine.

“The conventional way of thinking assumes that the individual has primary control over their calorie balance, and thus, bases conventional treatment on a target of establishing a negative energy balance – so that is 1,000 variations of the ‘eat less, move more’ recommendation,” Dr. Ludwig said in an interview.

The alternative to that established view has proven controversial. The Endocrine Society, in a recent scientific statement, said diet’s effect on obesity risk is largely explainable by calorie intake, rather than some special adverse effect on internal metabolism or energy expenditure.

“Stated differently, ‘a calorie is a calorie,’ ” the authors of the scientific statement said. “Thus, habitual consumption of highly palatable and energy-dense diets predispose to excess weight gain irrespective of macronutrient content.”

Others have sought to refute the carbohydrate-insulin hypothesis in recent reviews, such as an invited commentary in JAMA Internal Medicine by Kevin D. Hall, PhD, of the National Institute of Diabetes and Digestive and Kidney Diseases, and his coauthors.

“Although it is plausible that variables related to insulin signaling could be involved in obesity pathogenesis, the hypothesis that carbohydrate-stimulated insulin secretion is the primary cause of common obesity via direct effects on adipocytes is difficult to reconcile with current evidence,” Dr. Hall and his coauthors wrote in the commentary (JAMA Intern Med. 2018 Jul 2. doi: 10.1001/jamainternmed.2018.2920).

The conventional calorie balance model is a “straw man” that omits neuroendocrine mechanisms known to regulate homeostasis, added Dr. Hall and his coauthors, stating that accurate models of obesity should include physiological processes resisting weight loss and promoting weight gain.

“They might claim that this is a straw man argument, but I would claim that there is a case of the emperor’s new clothing,” Dr. Ludwig countered in the interview. “They argue that body weight is controlled by biology, and that that’s recognized in the conventional view, but how does that view inform treatment in any way? In the absence of any specific testable hypotheses for why the obesity epidemic has emerged so suddenly, conventional recommendations inevitably resort to advice to ‘eat less and move more.’ ”

Dr. Ludwig and Dr. Ebbeling have both conducted research studies examining the carbohydrate-insulin model, or the view that a high-carbohydrate diet results in postprandial hyperinsulinemia and promotes deposition of calories in adipocytes, leading to weight gain through slowing metabolism, increased hunger, or both.

In a study published in the Lancet, Dr. Ludwig and his coinvestigators found that rats fed a high–glycemic index (GI) diet for 18 weeks had more body fat (97.8 grams vs. 57.3 grams; P = .0152) and less lean body mass versus rats fed a low-GI diet. Rats on the high-GI diet also had greater increases over time in blood glucose and plasma insulin after oral glucose. Similarly, mice on a high-GI diet had nearly twice the body fat of mice on low-GI diet, after 9 weeks of feeding (Lancet. 2004 Aug 28. doi: 10.1016/S0140-6736(04)16937-7).

“There’s no way to explain that finding in view of the conventional view that all calories are alike to the body,” Dr. Ludwig said.

“Contrary to prediction of the conventional model, the inherently lower energy density of low-fat diets does not spontaneously produce sustained weight loss. In fact, several recent meta-analyses found that low-fat diets are inferior to all higher-fat [and thus low-glycemic] comparisons. However, these studies characteristically rely on dietary counseling, a method with limitations for testing mechanistic hypotheses owing to varying levels of noncompliance over the long-term,” Dr. Ludwig and Dr. Ebbeling wrote.

Criticisms that claim to refute the carbohydrate-insulin hypothesis are based in part on misinterpretation of recent feeding studies, according to Dr. Ludwig and Dr. Ebbeling. Multiple studies testing whether or not high–glycemic load meals lead to increased fat storage have reported no meaningful differences between low-fat and low-carbohydrate diets. However, these short-term studies, mostly 2 weeks in duration, preclude definitive findings, according to the review.

That’s because the process of adapting to a high-fat diet after having consumed a high-carbohydrate diet takes weeks, which is a well-recognized phenomenon, Dr. Ludwig said.

“If you put sedentary people into military boot camp and tested their biological state after 6 days, you’d probably find that they were fatigued, weak, and had higher inflammation in their muscles, but clearly, you wouldn’t conclude that fitness training is bad for your health,” he said in the interview. “But yet, these are the sort of data that are being used to ‘falsify’ the carbohydrate-insulin model.

“We acknowledge that there aren’t definitive human data,” he continued, “but the conventional model has failed to both explain the obesity epidemic and control it, and the latest public health data suggests that rates are higher today than ever before, despite 50 years of focusing on calorie balance.”


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